US6335792B1 - Method and apparatus for measuring internal property distribution in scattering medium - Google Patents

Method and apparatus for measuring internal property distribution in scattering medium Download PDF

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US6335792B1
US6335792B1 US09/716,264 US71626400A US6335792B1 US 6335792 B1 US6335792 B1 US 6335792B1 US 71626400 A US71626400 A US 71626400A US 6335792 B1 US6335792 B1 US 6335792B1
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absorption coefficient
medium
measured
reference value
weight function
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Yutaka Tsuchiya
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Hamamatsu Photonics KK
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/47—Scattering, i.e. diffuse reflection
    • G01N21/4795—Scattering, i.e. diffuse reflection spatially resolved investigating of object in scattering medium

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  • the present invention relates to a method for measuring an internal property distribution in a scattering medium and an apparatus therefor. More specifically, the present invention concerns a measuring method of internal property distribution and is applicable to equipment for obtaining internal information while moving a light injection position and a light detection position along a surface of a measured object, and an apparatus therefor.
  • Optical CT computer tomography
  • Optical CT means a technique or apparatus of measuring an optical property distribution or a concentration distribution of an absorptive constituent in an organism, and makes use of light (signal light) detected after injection of light into a living tissue and migration therethrough.
  • the practical optical CT needs to utilize the scattered light because of the limitations including maximum permissible incidence power to organisms, measurement sensitivity, required measurement time, and so on, but the above optical CT does not have been put into practical use yet because of the following technological problems.
  • the first problem is that no method has been developed for describing the behavior of light or a photon in a scattering medium with sufficient accuracy.
  • the diffusion approximation holds only in sufficiently larger media than the mean free path length of photons therein and is thus incapable of handling relatively small media, tissues having complicated internal shapes, and media having complicated shapes.
  • the diffusion approximation is predicated on isotropic scattering; therefore, when applied to measurement of actual living tissues having anisotropic scattering characteristics, it gives rise to unignorable errors due to the anisotropic scattering.
  • the diffusion equation does not allow us to find its solution by either of analytical or numerical techniques (such as the finite element method or the like) unless boundary conditions are preliminarily set. Namely, it is necessary to set the boundary conditions at each of the light injection and detection positions, i.e., the shape of the medium and reflection characteristics at interfaces, prior to measurement. If these conditions vary depending upon individual differences etc., computation must be redone under boundary conditions modified according to the variation. Therefore, the optical CT making use of the relation between signal light and optical properties of a scattering medium derived from the approximate expression of the transport equation or the photon diffusion equation still has a significant problem in accuracy and operability.
  • the second problem is that the conventional optical CT makes use of a weight function in a narrow sense, i.e., a mean path length or a phase lag equivalent thereto. For this reason, it becomes extremely complicated to handle the mean path length of detected light varying depending upon absorption coefficients. It is thus usual practice to employ approximation, but use of approximation poses a significant problem of increase in errors.
  • Such methods making use of the weight function in a narrow sense are described, for example, in references listed below.
  • the conventional optical CT techniques do not allow us to obtain a reconstructed image with sufficient accuracy and still have significant issues in terms of spatial resolution, image distortion, quantitation, measurement sensitivity, required measurement time, and so on.
  • the important points for realizing optical CT are to clarify the behavior of light migrating in living tissues of strong scattering media, to clarify the relation between signal light detected and optical properties of scattering media (scattering absorbers) containing absorptive constituents, and to develop an algorithm for reconstructing an optical CT image by making use of the signal light and the relation.
  • the present invention has been accomplished in view of the above conventional issues and an object of the invention is to provide a method and an apparatus that permit measurement of an absorptive constituent with higher accuracy even when applied to the scattering media of inhomogeneous systems such as organisms or the like.
  • the inventors further developed the above knowledge found by the inventor, and discovered that the above object was accomplished by ⁇ circle around (3) ⁇ applying the aforementioned MBL to the inhomogeneous systems, ⁇ circle around (4) ⁇ deriving analytic expressions to indicate the relation between optical properties of inhomogeneous scattering media and signal light, ⁇ circle around (5) ⁇ deriving a weight function according to a different definition from the conventional one from the relation between signal light and optical properties of inhomogeneous scattering media, and ⁇ circle around (6) ⁇ providing an algorithm and an apparatus for reconstructing an optical CT image by use of this weight function, whereby the inventors reached the invention.
  • a method for measuring an internal property distribution of a scattering medium according to the present invention is a method comprising:
  • a light injection step of successively injecting rays from at least one light injection position into a medium to be measured, which is a scattering medium;
  • an absorption coefficient absolute value computation step of computing an absolute value of the absorption coefficient in each voxel, based on the reference value of the absorption coefficient and the deviation of the absorption coefficient, to obtain a distribution of absolute values of absorption coefficients in the medium to be measured.
  • An apparatus for measuring an internal property distribution of a scattering medium is an apparatus comprising:
  • light injection means for successively injecting rays from at least one light injection position into a medium to be measured, which is a scattering medium
  • light detection means for detecting rays having passed through the interior of the medium to be measured, at a plurality of light detection positions
  • measurement value acquisition means for acquiring a measurement value of a predetermined parameter of the rays for each of combinations of the light injection position with the light detection positions, based on each ray detected;
  • reference value setting means for setting a reference value of an absorption coefficient of the medium to be measured
  • estimate computation means for computing an estimate of the parameter for each of the combinations of the light injection position with the light detection positions, based on the reference value of the absorption coefficient, on the assumption that the medium to be measured has the homogeneous reference value of the absorption coefficient as a whole;
  • weight function operation means for obtaining a weight function in each voxel of the medium to be measured, the medium being divided into a plurality of voxels, based on the Microscopic Beer-Lambert Law, using the homogeneous reference value of the absorption coefficient;
  • absorption coefficient deviation computation means for computing a deviation of the absorption coefficient from the reference value of the absorption coefficient in each voxel, based on the measurement value of the parameter, the estimate of the parameter, and the weight function;
  • absorption coefficient absolute value computation means for computing an absolute value of the absorption coefficient in each voxel, based on the reference value of the absorption coefficient and the deviation of the absorption coefficient, to obtain a distribution of absolute values of absorption coefficients in the medium to be measured.
  • the weight function in each voxel which is first disclosed by the present invention, is directly gained based on the MBL, and the deviation of the absorption coefficient in each voxel is computed based on the weight function, the measurement value of the predetermined parameter, and the estimate of the parameter.
  • the weight function is expressed by an equation of one kind regardless of the measurement circumstances. Since in the present invention the deviation of the absorption coefficient is computed based on the appropriate weight function even with variations in the individual measurement circumstances as described above, the invention prevents errors from being caused by employment of the approximation.
  • a preferred weight function adopted in the above method and apparatus of the present invention is a function of the mean path length in each voxel and the variance of the distribution of path lengths, on the assumption that the medium to be measured has the homogeneous reference value of the absorption coefficient as a whole.
  • the method further comprise the mean path length acquisition step (or the mean path length acquisition means) of acquiring the mean path length in each voxel, based on the reference value of the absorption coefficient, on the assumption that the medium to be measured has the homogeneous reference value of the absorption coefficient as a whole, and that the aforementioned weight function operation step comprise (or the weight function operation means perform) a step of gaining the weight function, based on the following equation:
  • W i is the weight function
  • Z i ( ⁇ av ) the mean path length
  • ⁇ ai the deviation of the absorption coefficient
  • ⁇ iv 2 the variance of the distribution of path lengths
  • Another preferred weight function adopted in the above method and apparatus of the present invention is a function of the mean path length in a predetermined time domain in each voxel and a variance of a distribution of path lengths, on the assumption that the medium to be measured has the homogeneous reference value of the absorption coefficient as a whole.
  • the method further comprise the mean path length acquisition step (or the mean path length acquisition means) of obtaining the mean path length in a predetermined time domain in each voxel, based on the reference value of the absorption coefficient, on the assumption that the medium to be measured has the homogeneous reference value of the absorption coefficient as a whole, and that the aforementioned weight function operation step comprise (or the weight function operation means perform) a step of gaining the weight function, based on the following equation:
  • W i is the weight function
  • Z i ( ⁇ av ) the mean path length
  • ⁇ ai the deviation of the absorption coefficient
  • ⁇ iv 2 the variance of the distribution of path lengths
  • still another preferred weight function adopted in the above method and apparatus of the present invention is a function of a group delay in each voxel and a variance of a distribution thereof, on the assumption that the medium to be measured has the homogeneous reference value of the absorption coefficient as a whole.
  • the weight functions are computed in consideration of not only the mean path length or the group delay varying depending upon the absorption coefficient, but also the variance of distribution thereof, there is a tendency to attain further improvement in the measurement accuracy of the internal property distribution obtained by use of such weight functions.
  • the method and apparatus of the present invention may further comprise a concentration computation step (or concentration computation means) of computing a concentration of an absorptive constituent in each voxel by using the absolute value of the absorption coefficient, and thus obtaining a concentration distribution of the absorption constituent in the medium to be measured. Since concentrations of the absorptive constituent can be obtained based on the absorption coefficient deviations determined accurately as described above by such method and apparatus, the concentration distribution can be obtained with high accuracy.
  • the rays injected into the measured medium in the light injection step have at least two wavelengths at which said absorptive constituents demonstrate their respective absorption coefficients different from each other.
  • each of the rays having the at least two wavelengths is detected in the light detection step (or by the light detection means), the measurement value is acquired as to each of the rays having the at least two wavelengths in the measurement value acquisition step (or by the measurement value acquisition means), the reference value is set as to each of the rays having the at least two wavelengths in the reference value setting step (or by the reference value setting means), the estimate is computed as to each of the rays having the at least two wavelengths in the estimate computation step (or by the estimate computation means), the weight function is gained as to each of the rays having the at least two wavelengths in the weight function operation step (or by the weight function operation means), the deviation of the absorption coefficient is computed as to each of the rays having the at least two wavelengths in the absorption coefficient deviation computation step (or by the absorption coefficient deviation computation means), the absolute value of the absorption coefficient is computed as to each of the rays having the at least two wavelengths in the absorption coefficient absolute value computation step (or by the absorption
  • the method and apparatus of the present invention described above may further comprise an image display step (or image display means) of displaying an optical CT image to indicate the distribution in the measured medium, based on the aforementioned distribution obtained.
  • the method and apparatus of the present invention in this structure can display the optical CT image with high accuracy by imaging of the internal property distribution obtained with accuracy as described above.
  • FIG. 1 is a schematic diagram to show a model concerning photon migration in an inhomogeneous medium.
  • FIG. 2 is a schematic diagram to show an embodiment of the apparatus for measuring an internal property distribution of a scattering medium according to the present invention.
  • FIG. 3 is a flowchart to show an embodiment of the method for measuring an internal property distribution of a scattering medium according to the present invention.
  • FIG. 4 is a flowchart to show an embodiment of an operation method for gaining the weight function according to the present invention.
  • FIG. 5 is a graph to show an absorption coefficient distribution (a relation between reference value of absorption coefficient and deviation of absorption coefficient) in each voxel.
  • FIG. 6 is a graph to show absorption spectra of hemoglobin and myoglobin.
  • the present invention employs novel weight functions derived based on the Microscopic Beer-Lambert Law.
  • the weight functions according to the present invention are different from the conventional weight functions, i.e., from photon path lengths and the mean path length in each voxel (volume element), photon residence time, phase delays corresponding thereto, and so on.
  • the weight functions adopted in the present invention are expressed in the from involving the medium shape, the boundary conditions, the light incidence and detection positions, the distance between them, the scattering coefficient of the medium, and so on. These weight functions are uniquely determined against a scattering medium. Since in the present invention the optical CT image is reconstructed using the weight functions as described above, the errors, which were the problem heretofore, are reduced greatly as described hereinafter, whereby the optical CT image can be obtained with high accuracy.
  • the scattering medium has an arbitrary three-dimensional shape that never permits reentry of emergent light. Therefore, no photon emerging from the medium is incident again into the medium.
  • the boundary conditions between the scattering medium and an external medium for example, matching conditions of shape and refractive index, can be determined on an optional basis.
  • Macroscopic refracting properties are uniform (homogeneous). However, absorption coefficient distribution is not uniform (inhomogeneous). Such a medium will be called hereinafter an inhomogeneous medium or an inhomogeneous system for convenience sake. Therefore, the speed of light in the scattering medium, discussed below, is a constant c.
  • This scattering medium assumed to absorb no photon is called an “imaginary medium.”
  • the whole three-dimensional inhomogeneous medium having the inhomogeneous distribution of absorption (or an absorptive constituent) is divided into N voxels, a number i is assigned to each voxel, and an anisotropic scattering coefficient ⁇ s , a mean cosine of scattering angles g, and an absorption coefficient ⁇ ai are defined for each voxel i (reference is made to FIG. 1 ).
  • the photon injection-detection positions are p(u, v).
  • ⁇ s and ⁇ ai are values inherent in the inhomogeneous medium, ⁇ s is a constant, and ⁇ ai is a function of position.
  • the voxel i may have arbitrary size and shape and a voxel of a large volume can be handled noting an average absorption coefficient or the mean path length in that voxel. Further, two or more voxels spatially apart from each other may also be considered together as one voxel.
  • l im is determined uniquely.
  • the absorption coefficient ⁇ ai of that voxel i is determined uniquely. In this case, because the absorption coefficient is under optional selection, the photon path length and absorption coefficient of voxel are independent of each other.
  • the attenuation (which is also called an extinction amount) B m of the m-th photon detected at the time t is given by the following equation.
  • This relation represents connection of MBL at the positions of change in the absorption coefficients during the photon migration. This relation also holds when the zigzag photon path makes intersections (where the photon passes the same place two or more times).
  • An impulse response includes photons having various path lengths.
  • the weight functions W i are dependent upon absorption.
  • the MBL for the inhomogeneous system will be derived by obtaining various responses in the inhomogeneous system.
  • the light injection-detection positions are set as p(u, v) for the inhomogeneous medium.
  • An attenuation of each of the various responses is superposition of attenuations of single photons constituting each of the various responses.
  • the impulse response h(t) of the inhomogeneous system is comprised of a lot of detected photons having various path lengths.
  • the impulse response under ⁇ a 0, i.e., the term s( ⁇ s , t) to indicate the effects of the medium shape and scattering, is separated from the term B h to indicate the attenuation dependent upon absorption, as stated previously.
  • analytic equations will be first derived for the time-resolved gate integration signal of the impulse response of the inhomogeneous system and then the weight functions will be derived taking account of absorption dependency of attenuation and mean path length.
  • the integration range of time domain [t 1 , t 2 ] is set to [0, ⁇ ]
  • the response represents one to stationary (CW) light.
  • I T The time-resolved gate integration signal I T of the impulse response is expressed below as a result of integration of Eq. (3.1.8).
  • This L i ( ⁇ a ) is dependent upon the scattering property of the medium, the boundary conditions, and t 1 , t 2 .
  • L i ( ⁇ a ) is a monotone non-increasing function against ⁇ ai .
  • the first term on the right side indicates no relation with absorption, i.e., does the effects of scattering and boundary
  • the second term on the right side indicates the attenuation B T .
  • L i ( ⁇ a ) of the voxel i of interest is determined roughly by an average of the absorption coefficients of all the voxels and a change of L i ( ⁇ a ) dependent upon the deviations of the absorption coefficients of the other portions from the average absorption coefficient is negligibly small. Therefore, L i ( ⁇ a ) can be regarded as a function of only the absorption coefficient ⁇ ai of the voxel i.
  • L i ( ⁇ a ) is a function of only the absorption coefficient ⁇ ai of the voxel i. Namely, where the mean path length L i ( ⁇ a ) of the voxel i is of interest, it is assumed that the parameters other than the absorption coefficient ⁇ ai of the voxel i are constant (invariant).
  • This equation indicates the MBL for the photon assemblage constituting the time-resolved gate integration signal I T of the inhomogeneous system. It is, however, noted that the aforementioned linear approximation was applied.
  • the equation represents MBL for the ordinary time-resolved integration signal, i.e., for the stationary (CW) light.
  • ⁇ x0 is an appropriate value to satisfy 0 ⁇ x0 ⁇ ai .
  • Eq. (3.2.5) needs to be used instead of Eq. (3.2.6) where the aforementioned dependency of L i ( ⁇ a ) on the absorption of all the voxels is significant.
  • the above can also be applied to the ordinary time-resolved integration signal, i.e., the response to the stationary (CW) light by setting the integration range [t 1 , t 2 ] to [0, ⁇ ].
  • the mean path length of each voxel is dependent on absorption of the voxel.
  • the weight function is also dependent on the absorption of the voxel.
  • the attenuation B iT of the voxel i indicated by Eq. (3.2.7.2) can be expressed as follows in the form of Taylor series with respect to ⁇ ai .
  • B iT ⁇ ( ⁇ ai + h ) B iT ⁇ ( ⁇ ai ) + h 1 ! ⁇ ⁇ B iT ( 1 ) ⁇ ( ⁇ ai ) + h 2 2 ! ⁇ ⁇ B iT ( 2 ) ⁇ ( ⁇ ai ) + ⁇ (3.2.8)
  • B iT (n) ( ⁇ a ) is the n-th order derivative of B iT ( ⁇ a ) with respect to ⁇ a . From the relation of Eq. (3.2.6), the following is obtained.
  • B iT (2) ( ⁇ ai ) is gained as follows using Eq. (3.2.2).
  • B iT ⁇ ( ⁇ ai + h ) B iT ⁇ ( ⁇ ai ) + hL i ⁇ ( ⁇ ai ) - h 2 2 ⁇ ⁇ ⁇ i 2 ⁇ ( l iT ) + ⁇ (3.2.11)
  • a difference ⁇ B iT between attenuations before and after change of the absorption coefficient from ⁇ ai to ( ⁇ ai +h) is obtained as follows from Eq. (3.2.7.2).
  • This ⁇ x is different from aforementioned ⁇ x0 and is an appropriate value to satisfy the condition of min( ⁇ ai , ⁇ ai +h) ⁇ x ⁇ max( ⁇ ai , ⁇ ai +h).
  • This L i ( ⁇ x ) is the weight function W i against the difference ⁇ B iT of attenuation.
  • L i ( ⁇ ai ) can be written as follows in the form of Taylor series with respect to ⁇ ai .
  • L i ⁇ ( ⁇ ai + h ) L i ⁇ ( ⁇ ia ) + h 1 ! ⁇ ⁇ L i ( 1 ) ⁇ ( ⁇ ai ) + h 2 2 ! ⁇ ⁇ L i ( 2 ) ⁇ ( ⁇ ai ) + ⁇ (3.2.14)
  • L i (n) ( ⁇ a ) is the n-th order derivative of L i ( ⁇ a ) with respect to ⁇ a . Therefore, the following is gained from Eq. (3.2.13) and Eq. (3.2.14).
  • the accuracy is improved when the absorption coefficients ⁇ ai are selected so as to be equal or close to the average absorption coefficient of the medium to be measured. Namely, the problem of dependency of L i ( ⁇ a ) on the absorption of all voxels as stated previously is relaxed greatly.
  • the above can be applied to the ordinary time-resolved integration signal, i.e., to the response to the stationary (CW) light by setting the integration range [t 1 , t 2 ] to [0, ⁇ ].
  • the optical CT is an approach to measurement of concentration distribution of absorptive constituents in the inhomogeneous media.
  • problems are made complex by the aforementioned two types of absorption dependency of the mean path length, i.e., the dependency of L i ( ⁇ a ) on absorption of all voxels and the dependency of L i ( ⁇ a ) on absorption of the voxel i itself.
  • the inventors developed the Average Value Method (hereinafter referred to as “AVM”) as a method for reducing errors based on these absorption dependencies.
  • AVM Average Value Method
  • This AVM is a method of estimating or measuring an approximate average absorption coefficient for an inhomogeneous medium to be measured and quantitating a deviation of the absorption coefficient in each part of the medium, with respect to this average value.
  • the average absorption coefficient estimated or measured above does not have to be equal to a true value.
  • This method greatly relaxes the problem of the absorption coefficient dependency of the mean path length and improves the accuracy of reconstructed optical CT image more and more as the average absorption coefficient estimated or measured above becomes closer and closer to the true value.
  • the absorption coefficient deviations ⁇ ai of plural voxels i can be gained from the difference ⁇ I between time-resolved gate integration signals lnI T of impulse responses to the imaginary medium and the actual medium, and the weight function W i under the absorption coefficient of ⁇ av .
  • the mean path length and variance of the voxel i of the medium (imaginary medium) demonstrating the uniform absorption as described above can be computed by Monte Carlo simulations and the like.
  • R, X, A, and ⁇ are defined as follows.
  • A ( R 2 + X 2 ) 1 2 (3.3.2.3)
  • ⁇ - tan - 1 ⁇ ⁇ X R (3.3.2.4)
  • R and X are the real part and the imaginary part, respectively, and A and ⁇ are the amplitude and phase dalay, respectively. These can be measured readily by a lock-in amplifier or the like.
  • Eq. (3.3.6.1) to Eq. (3.3.6.4) above are similar to the equations for time-resolved gate integration signal described in the previous section, these equations can be modified in a fashion similar to those in the previous section.
  • Eq. (3.3.6.3) will be discussed below as an example.
  • the weight functions for the response in the frequency domain as in the previous section.
  • the attenuation term of Eq. (3.3.6.3) (the second term in the right side) can be written as follows by use of the mean value theorem.
  • ⁇ x is an appropriate value to satisfy 0 ⁇ x ⁇ ai .
  • ⁇ ⁇ i ⁇ ⁇ (3.3.7.4) c ⁇ ⁇ ⁇ ⁇ i ⁇ ⁇ (3.3.7.5)
  • absorption coefficient dependencies of the attenuation B if and average group delay (3.3.7.4) of the voxel i are similar to those of the attenuation B iT and mean path length L i ( ⁇ x ) stated in the previous section. Namely, as to the absorption dependency of the group delay (3.3.7.4), it is derived as follows from Eq. (3.3.3.4) and Eq. (3.3.5.2).
  • the average group delay (3.3.7.4) is assumed to be independent of the group delays of the voxels other than the voxel i, i.e., independent of the following. ⁇ ⁇ j ⁇ ⁇ ⁇ ⁇ ( j ⁇ i )
  • Eq. (3.3.3.3) to indicate the attenuation B f of the amplitude A detected in measurement in the frequency domain, etc. are expressed in the differential form and those equations are similar.
  • the mean path length Z is a function of ⁇ ai .
  • Eq. (4.1) represents the general expression of MBL for the inhomogeneous systems. Namely, this Eq. (4.1) indicates that the attenuation in the inhomogeneous media is determined by only the absorption coefficient and the mean path length of each voxel. Therefore, the MBL for the inhomogeneous systems may be considered to be the description of this fact.
  • W i is the weight function of each voxel.
  • the mean path length and variance of the voxel i of the medium (imaginary medium) demonstrating the uniform absorption can be computed by Monte Carlo simulations or the like.
  • Z i ( ⁇ ai ) the dependency of Z i ( ⁇ ai ) on the absorption of all voxels as discussed previously poses a problem, it is necessary to perform such iterative computations as to return to Eq. (4.7) below and execute recalculation.
  • FIG. 2 shows an internal property distribution measuring system (optical CT image measuring device) 1 for measuring a concentration distribution of an absorptive constituent distributed inside a medium 10 to be measured, which is a scattering medium.
  • an internal property distribution measuring system 1 for measuring a concentration distribution of an absorptive constituent distributed inside a medium 10 to be measured, which is a scattering medium.
  • the light source 23 can be one selected from various sources including light emitting diodes, laser diodes, He-Ne lasers, and so on.
  • the light source 23 may be one of those generating pulsed rays, rectangular rays, or modulated rays thereof.
  • the light source 23 used in the present embodiment may be one generating rays of a single wavelength or one capable of generating rays of two or more wavelengths.
  • Each of the light detection fibers 25 is optically connected to a photodetector 26 and rays traveling through while being scattered in the measured medium 10 are guided through the light detection fibers 25 to the photodetectors 26 .
  • the photodetectors 26 convert their respective, received light signals into detection signals (electrical signals) and amplify the detection signals to output their respectively corresponding detection signals.
  • the photodetectors 26 can be selected from all types of photodetectors including photomultiplier tubes, phototubes, photodiodes, avalanche photodiodes, PIN photodiodes, and so on.
  • the point necessary for the selection of the photodetectors 26 is that the photodetectors have spectral sensitivity characteristics enough to detect light of the wavelength of the measurement light (measurement rays) used. When light signals are weak, it is preferable to use the photodetectors with high sensitivity or with high gain.
  • a wavelength selecting filter may also be properly placed between each pair of photodetector 26 and light detection fiber 25 if the rays having diffused and propagated inside the measured medium 10 include rays of plural wavelengths.
  • a CPU (control and processing unit) 30 is electrically connected to the light source 23 and to the photodetectors 26 .
  • the CPU 30 controls timing of light detection in synchronism with light injection, and other operations, and the detection signals outputted from the photodetectors 26 are guided to the CPU 30 .
  • the CPU 30 also controls the wavelengths of injected rays.
  • Specific control techniques include a technique of injecting and using rays of the different wavelengths in time-shared manner, and a technique of using light simultaneously including the rays of the different wavelengths.
  • Specific wavelength selecting means include a beam switch using a mirror, a wavelength switch using a filter, a light switch using an optical switch, and so on.
  • the above light injection fiber 21 , wavelength selector 22 , light source 23 , and CPU 30 constitute the light injection means according to the present invention
  • the above light detection fibers 25 , photodetectors 26 , and CPU 30 constitute the light detection means according to the present invention.
  • the internal property distribution measuring system 1 illustrated in FIG. 2 further has a first storage device 40 storing an operating system (OS) 41 and an internal property distribution measurement program 42 detailed hereinafter, a second memory device 50 storing various files, an image memory 61 for storing optical CT image data to indicate the internal property distribution obtained, a working memory 62 for temporarily saving working data, an input device 70 equipped with a keyboard 71 and a mouse 72 for entry of data, and an output device 80 equipped with a display 81 and a printer 82 for output of resultant data, which are also controlled by the CPU 30 electrically connected thereto.
  • the above storage devices and memories may be an internal memory (hard disk) of a computer or a flexible disk.
  • the second storage device 50 includes a basic path length distribution data file 51 , a measurement data file 52 , an input data file 53 , an absorption coefficient data file 54 , and an absorber concentration data file 55 .
  • the basic path length distribution data file 51 stores a basic path length distribution preliminarily prepared (which is a common path length distribution as a basis for the operation of various weight functions used in various measurements).
  • This basic path length distribution can be computed by making use of the known techniques, for example, by using the Monte Carlo simulations and the photon diffusion equation, which are described, for example, in the following references: (17) J. Haselgrove, J. Leigh, C. Yee, N-G, Wang, M. Maris and B. Chance: Proc. SPIE, Vol. 1431, 30-41 (1991); (18) J. C. Schotland, J. C. Haselgrove and J. S. Leigh: Appl. Opt.
  • Preset measurement conditions and known values are entered through the input device 70 and such input data is stored in the input data file 53 .
  • Such input data includes the arbitrarily preset number, shape, and size of voxels (volume elements), the shape of the measured medium, the light injection positions, the light detection positions, the scattering coefficient, the average absorption coefficient, the wavelength of rays used in measurement, the type of measurement (time-resolved integration measurement, time-resolved gate integration measurement, phase modulation measurement, etc.), an extinction ratio of an absorber as a measured object at a predetermined wavelength, and so on.
  • the measurement data file 52 stores measurement values of the predetermined parameter obtained, based on the detection signals from the photodetectors 26 , in an execution process of the internal property distribution measurement program 42 , in correspondence to combinations of the light injection positions with light detection positions.
  • the absorption coefficient data file 54 and the absorber concentration data file 55 store the absorption coefficient data and absorber concentration data obtained by execution of the internal property distribution measurement program 42 .
  • the above CPU 30 , first storage device 40 , and second storage device 50 constitute the measurement acquisition means, the reference value setting means, the estimate computation means, the weight function operation means, the absorption coefficient deviation computation means, the absorption coefficient absolute value computation means, and the concentration computation means according to the present invention, and the above output device 80 does the image display means.
  • These various means according to the present invention will be detailed below, based on a flowchart of an embodiment of the method of the present invention illustrated in FIG. 3 and FIG. 4 (which is a flowchart to indicate processing of the internal property distribution measurement program 42 illustrated in FIG. 2 ).
  • the combinations P n of the light injection-detection positions to the n sets of data are different from each other.
  • the measurement values Y n of the predetermined parameter according to the present invention are preferably measurement values of a predetermined parameter related to scattering and absorption of the measurement rays inside the measured object, and, for example, suitably applicable measurement values are those of such parameters as the light quantity, phase difference (or phase lag), amplitude, time-resolved waveform, etc. of the detected rays.
  • the CPU 30 can perform the time-resolved gate integration measurement if the integration operation of the light detection signals is carried out in a predetermined time range (t 1 ⁇ t 2 ) by making use of signals timed with generation of the rays from the light source 23 . On the other hand, it can also perform the ordinary time-resolved integration measurement if the integration range is set in 0 ⁇ . In the case of the pulsed rays etc. being used, the synchronous signals do not have to be used.
  • the CPU 30 may also be arranged to perform correction for the measurement values by making use of the averaging filtering, the least square fitting, or
  • the next step is to set a reference value ⁇ av of the absorption coefficient and a reference value ⁇ ′ s of the transport scattering coefficient of the measured medium 10 (S 104 ).
  • an average absorption coefficient (approximate value) from a macroscopic aspect of the measured medium 10 , i.e., that on the assumption that the measured medium 10 has the homogeneous absorption coefficient as a whole.
  • an average transport scattering coefficient (approximate value) on the assumption that the measured medium 10 has the homogeneous scattering coefficient as a whole.
  • Such absorption coefficient ⁇ av and transport scattering coefficient ⁇ ′ s can be obtained from the light detection signals (or the measurement values Y n of the predetermined parameter) detected at the aforementioned plurality of light detection positions v k .
  • the light detection signals are impulse responses (light detection signals against injection of pulsed light assumed to be sufficiently short relative to temporal waveforms of the light detection signals)
  • the absorption coefficient ⁇ av and transport scattering coefficient Ats of the interior of the medium corresponding to a predetermined light injection-detection position combination P n can be obtained by fitting the temporal waveforms to the photon diffusion equation.
  • another average optical constant may also be obtained further from the macroscopic aspect of the measured medium 10 , and examples of such an optical constant include the refractive index n e of the measured medium, the scattering coefficient ⁇ s , and the average cosine g of scattered angles.
  • the refractive index n e of the measured medium can be normally approximated to that of water.
  • the estimate of the predetermined parameter (of the light detection signal) in each light injection-detection position combination P n can be yielded, for example, by solving the photon diffusion equation with provision of the above average optical constants (the reference value ⁇ av of the absorption coefficient, the reference value ⁇ ′ s of the transport scattering coefficient, etc.).
  • the result with change of an optical constant from the result of Monte Carlo calculation with provision of any given optical constant (for example, absorption coefficient) (for example, as described in A. Kienle and M. S. Patterson: Phys. Med. Biol. 41, 2221-2227 (1996)).
  • the mean path length Z i ( ⁇ av ) in each voxel i of the measured medium 10 divided into a plurality of voxels is acquired, based on the reference value ⁇ av of the absorption coefficient, on the assumption that the measured medium 10 has the homogeneous reference value ⁇ av of the absorption coefficient as a whole (S 106 ).
  • the basic path length distribution preliminarily determined by the Monte Carlo calculation or the like is read out of the basic path length distribution data file 51 and, based on the reference value ⁇ av of the absorption coefficient and the reference value ⁇ ′ s of the transport scattering coefficient, the path length distribution of detected rays can be determined for the imaginary medium having th ese reference values.
  • This is conversion of the basic path length distribution, which can be carried out using the method described in (24) A. Kienle and M. Patterson: Phys. Med. Biol. 41, 2221-2227 (1996), for example.
  • the estimate Y avn of the predetermined parameter (of the light detection signal) in each light injection-detection position combination P n can also be computed based on the path length distribution Z i ( ⁇ av ) of detected rays for the imaginary medium, obtained herein.
  • a flow of processing in this case is indicated by a chain line A in FIG. 3 .
  • the weight function W i in each voxel i is computed according to Eq. (4.6) in conformity with the Microscopic Beer-Lambert Law (S 107 ), and then, based on the measurement values Y n and estimates Y avn of the predetermined parameter in the respective light injection-detection position combinations P n and the weight functions W i , the deviation ⁇ ai of the absorption coefficient from the reference value ⁇ av of the absorption coefficient in each voxel i is computed according to Eq. (4.5) (S 108 ).
  • FIG. 4 is a flowchart to show a preferred embodiment of the processing for obtaining the weight functions W i and absorption coefficient deviations ⁇ ai by such iterative operations. The flowchart illustrated in FIG. 4 will be detailed below.
  • the weight function W iK is determined according to Eq. (4.6), based on the mean path length Z i ( ⁇ av ) and absorption coefficient deviation ⁇ aiK in each voxel i (S 202 ).
  • ⁇ iv 2 in Eq. (4.6) represents the variance and is obtained, for example, by computation of Eq. (3.2.10) or Eq. (3.3.8).
  • the deviation ⁇ ai (K+1) of the absorption coefficient in each voxel i is computed according to Eq. (4.5), based on the measurement values Y n and estimates Y avn of the predetermined parameter and the weight functions W iK (S 203 ).
  • a residual E is computed between the deviation ⁇ ai (K+1) of the absorption coefficient obtained in S 203 and the absorption coefficient deviation ⁇ aiK used in S 202 (S 204 ), and it is determined whether the value thereof is not more than a predetermined value (err) (S 205 ).
  • the weight functions W iK at that time are outputted as the weight functions W i and the absorption coefficient deviations ⁇ ai (K+1) at that time as the absorption coefficient deviations ⁇ ai (S 206 ).
  • the absorption coefficient deviations ⁇ aiK used in S 202 are replaced by the absorption coefficient deviations ⁇ ai (K+1) gained in aforementioned S 203 (an increment of 1 is given to the order K: S 207 ), and the operation of the weight functions W iK (S 202 ), the operation of the absorption coefficient deviations ⁇ ai (K+1) (S 203 ), and the operation of the aforementioned residual E (S 204 ) are carried out again.
  • FIG. 5 shows the relationship among the reference value ⁇ av , the deviations ⁇ ai , and the absolute values ⁇ ai of absorption coefficients. Then a distribution concerning the absolute values of absorption coefficients in the interior of the measured medium is obtained based on the absolute value ⁇ ai of the absorption coefficient in each voxel i obtained as described above, and an optical CT image to indicate the distribution is displayed at the output device 80 (S 110 ).
  • ⁇ indicates an absorption coefficient (or extinction coefficient) per unit concentration of the absorber, which can be measured by a spectrophotometer.
  • concentration C i in each voxel i of the aforementioned absorber is given by the following equation derived from the Beer-Lambert Law;
  • the concentration C i of the absorber in each voxel i can be computed from the above absolute value ⁇ ai of the absorption coefficient in each voxel i, using the known absorption coefficient of the absorber (S 111 ), and is stored in the absorber concentration data file 55 . Then a distribution concerning concentrations of the absorber in the interior of the measured medium is obtained based on the concentration C i of the absorber in each voxel i thus obtained, and an optical CT image to indicate the distribution is displayed at the output device 80 (S 112 ).
  • Deviations and absolute values of concentrations of two or more kinds of absorbers can also be measured using rays of two or more wavelengths in the above method of the first embodiment.
  • the present embodiment illustrates a two-wavelength spectroscopic measurement method for measurement with two types of rays of the wavelengths ⁇ 1 and ⁇ 2 . Namely, if absorption coefficients (or extinction coefficients) ⁇ 1 and ⁇ 2 per unit concentration of each absorber corresponding to the rays of the wavelengths ⁇ 1 and ⁇ 2 are known, two equations hold as to aforementioned Eq. (C.2) and Eq. (C.3). W i the simultaneous system of these equations, it is thus possible to measure the deviations and absolute values of concentrations of the two types of absorbers.
  • the distribution of concentrations C i of each absorptive constituent can be obtained by using the measurement rays having at least two wavelengths at which the absorptive constituents demonstrate their respective absorption coefficients different from each other, gaining the measurement values Y n , estimates Y avn , reference value ⁇ av , and weight functions W i for each of the measurement rays having the respective wavelengths, and computing the absorption coefficient deviations ⁇ ai and absorption coefficient absolute values ⁇ ai for each of the measurement rays having the respective wavelengths, based thereon.
  • absorptive constituents for example, oxygenated and deoxygenated hemoglobins
  • the principal absorptive constituents in mammalian brain are water, cytochrome, and oxygenated and deoxygenated hemoglobins. Absorption of water and cytochrome in the near-infrared region is as little as almost negligible with respect to that of oxygenated and deoxygenated hemoglobins.
  • the oxygenated and deoxygenated hemoglobins demonstrate different absorption spectra, as illustrated in FIG. 6 . Further, the cranial bones can be considered to be scattering media against near-infrared rays.
  • ⁇ a1 ⁇ Hb,1 [Hb]+ ⁇ HbO,1 [HbO]
  • ⁇ a2 ⁇ Hb,2 [Hb]+ ⁇ HbO,2 [HbO]
  • ⁇ Hb,1 molar absorption coefficient [mm ⁇ 1 .M ⁇ 1 ] of deoxygenated hemoglobin at wavelength ⁇ 1 ;
  • ⁇ HbO,1 molar absorption coefficient [mm ⁇ 1 .M ⁇ 1 ] of oxygenated hemoglobin at wavelength ⁇ 1 ;
  • ⁇ Hb,2 molar absorption coefficient [mm ⁇ 1 .M ⁇ 1 ] of deoxygenated hemoglobin at wavelength ⁇ 2 ;
  • ⁇ HbO,2 molar absorption coefficient [mm ⁇ 1 .M ⁇ 1 ] of oxygenated hemoglobin at wavelength ⁇ 2 ;
  • the molar concentration [Hb] of deoxygenated hemoglobin and the molar concentration [HbO] of oxygenated hemoglobin can be acquired from the known parameters ⁇ Hb,1 , ⁇ HbO,1 , ⁇ Hb,2 , ⁇ HbO,2 and the values ⁇ a1 and ⁇ a2 computed from the measurement values.
  • rays of three or more wavelengths can be used for quantitation of concentrations of the three components whose absorption spectra are known.
  • quantitation of concentrations of n components whose absorption spectra are known can be implemented in similar fashion to the above, from measurement values of absorption coefficients at n or (n+1) wavelengths.
  • the saturation degree Y can be computed readily from the known parameters ⁇ Hb,1 , ⁇ HbO,1 , ⁇ Hb,2 , ⁇ HbO,2 and the values ⁇ a1 and ⁇ a2 computed from measurement values, using the following equation.
  • ⁇ a1 / ⁇ a2 ⁇ [ ⁇ Hb , 1 + Y ⁇ ( ⁇ HbO , 1 - ⁇ Hb , 1 ) ] ⁇ ⁇ [ ⁇ Hb , 2 + Y ⁇ ( ⁇ HbO , 2 - ⁇ Hb , 2 ) ]
  • each of the concentrations can also be gained with high accuracy. It is also noted that the above equation will be simplified further by use of the wavelength (800 nm isosbestic wavelength) at which the oxygenated and deoxygenated hemoglobins demonstrate an equal absorption value.
  • the present embodiment illustrates an example of application of the present invention to the phase modulation measurement.
  • the measurement values Y n , estimates Y avn , reference value ⁇ av , and weight functions W i are obtained in the same manner as in the first embodiment except that the incident rays in the first embodiment are replaced by amplitude-modulated rays, the predetermined parameter by the amplitude A and phase lag ⁇ of detected rays, the path length distribution Z i ( ⁇ av ) of detected rays by a distribution of c (the speed of light in the medium) times group delay defined below: ⁇ c ⁇ ⁇ ⁇ ⁇ i ⁇ ⁇ ⁇ ⁇ av ;
  • ⁇ f 2 indicates the variance of the distribution. Further, the basic path length distribution in the first embodiment is replaced by the c times group delay distribution.
  • the reference value of absorption coefficient and the reference value of transport scattering coefficient were determined from the data acquired by the optical CT system itself in the above embodiments, but these reference values may also be acquired by another device.
  • An advantage in this case is a simpler system configuration of the optical CT apparatus, because it permits the data acquired by the optical CT apparatus to be measured with CW (continuous rays) and also permits the pulsed rays or modulated rays to be used only in the device for acquiring the above reference values.
  • Techniques for attaining the above reference values by another device may be the phase modulation method and the time-resolved spectroscopy.
  • the apparatus was arranged to move the light injection position, but the apparatus may also be modified so as to move the light detection position in synchronism with the light injection position.
  • the apparatus may also be modified in such structure that a plurality of light injection fibers and a plurality of light detection fibers are arranged around the measured medium and that the light injection position is moved by successively selecting the fibers used for injection of light.
  • apparatus and methods of the present invention described above can also be applied to apparatus and methods for three-dimensionally measuring an absorptive constituent inside a three-dimensional medium, without having to be limited to the optical CT for obtaining ordinary tomographic images. It is also obvious that the apparatus and methods of the present invention can be applied to measurement of media having laminar structure of many layers, such as the head skin, cranial bones, gray matter, and white matter. In this case, the layers can be considered in correspondence to the respective voxels.
  • the present invention allows the weight functions in the respective voxels to be gained directly based on the Microscopic Beer-Lambert Law in each of individual measurements by use of the new weight functions and thus allows the deviations of absorption coefficients to be computed based on the proper weight functions according to the measurement circumstances, thereby preventing the rise of errors due to employment of approximation. For that reason, the present invention enables the deviations of absorption coefficients in the voxels to be gained accurately even when applied to the scattering media of such inhomogeneous systems as organisms and also enables the highly accurate internal property distribution to be gained based on such absorption coefficient deviations and to be imaged as an optical CT image.
  • the present invention enables the distribution of an absorber or absorbers in the interior of various scattering media having various contours permitting no reentry of light to be measured with high accuracy and quickly, and can also be applied, for example, to photo-mammography, optical CT of head, optical CT for the entire body, clinical monitors, diagnosis and analysis, and operations and cures.

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Reconstructuring Absorber Images in a Three-Dimensional Scattering Medium by Using Photon-Path Data, A. Maki et al., pp. 299-304 (discussed at p. 5 of specification).
The Forward and Inverse Problems in Time Resolved Infra-Red Imaging, S. Arridge, pp. 35-64 (p. 5 of specification).
Time-Resolved Transillumination for Medical Diagnostics, R. Berg et al., pp. 110-119 (p. 72 of specification).
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AU3850999A (en) 1999-12-13
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